Rings and Steroelectronics

Question 1

What are conformers?

Answer 1

structures that differ only by rotation

Question 2

What are conformations?

Answer 2

different spatial arrangements a molecule can adopt due to rotation around single bonds

Question 3

What are enantiomers?

Answer 3

molecules that are non-superimposable mirror images of each other (R/S constant)

Question 4

what are diasteroisomers?

Answer 4

molecules that are superimposable mirror images of each other (R/S changes)

Question 5

why are eclipsed formations higher in energy than staggered

Answer 5

more steric hinderance in eclipsed formations as substituents lie on top of each other

Question 6

name 4 factors that contribute to conformational energy

Answer 6

hyperconjugation, pitzer strain, sterics and hydrogen bonding

Question 7

how does hyperconjugation stabilise

Answer 7

sigma-sigma star overlap which stabilises staggered conformations

Question 8

how does pitzer strain effect conformations

Answer 8

pitzer strain is electrostatic repulsion between electrons in filled orbitals. this destabilises eclipsed conformations

Question 9

how does hydrogen bonding effect conformations

Answer 9

it stabilises synclinal and synperiplanar conformations as hydrogen bonds could be formed between substituent groups

Question 10

What is the equation used to find A values from equilibrium constants

Answer 10

A=-RTln(K)
giving K=e(-A/RT)

Question 11

What is Baeyer strain

Answer 11

strain when atoms are distorted from their ideal bond angles in order to form a ring

Question 12

What is transannular strain

Answer 12

only effects medium size rings, happens when substituents point at each other across leading leading to additional strain

Question 13

Describe cyclopropanes bonding

Answer 13

has high Pitzer strain due to the C-C bonds being eclipsed
high Baeyer strain as bond angles are pushed smaller than ideal. causing carbon atoms to rehybridize and C-C bonds distort into banana bonds

Question 14

What is the rule when rings are formed

Answer 14

rings will adopt the lowest energy conformation possible my minimising Baeyer and Pitzer strain

Question 15

Describe cyclobutanes bonding

Answer 15

the rings pucker to reduce overall energy, so no bonds are fully eclipsed which slightly minimises Pitzer strain but still very high.
puckering decreases bond angles which increases Baeyer strain

Question 16

What is cyclopentanes lowest energy conformation

Answer 16

takes an envelope conformation, has some Pitzer and Baeyer strain

Question 17

What is cyclohexanes lowest energy conformation

Answer 17

takes a chair conformation, all bonds are staggered so no ring strain

Question 18

What are some of cyclohexanes other conformers

Answer 18

has chair which is the lowest in energy, half-chairs which are the highest in energy, boat and twist-boat conformations also formed

Question 19

what do substituents do to cyclohexane conformations?

Answer 19

they still favour chair conformation but largest group goes equatorial in order to minimise 1,3-diaxial interactions

Question 20

How can cyclohexane be conformationally locked?

Answer 20

when the substituent is very large like tBu, its conformationally locked as tBu cannot be axial
also trans-decalin is conformationally locked as if switched, one ring looses its chair formation (cis-decalin is not locked though)

Question 21

How can we use the Karplus curve to relate J values to conformation

Answer 21

If the hydrogens considered are at 60-120 degrees to each other, theyll have low coupling between 2-5Hz
if the hydrogens being considered are on top of each other or 180 degrees to each other, theyll have high coupling constants from 10-13Hz.

Question 22

What is the anomeric position?

Answer 22

the position between an N/O in the ring and an EWG

Question 23

What is the anomeric effect?

Answer 23

electronegative groups at the anomeric position adopt an axial position due to strong hyperconjugation, although creates destabilising 1,3-diaxial interactions

Question 24

What is a general route to small and normal sized rings? Draw simple mechanism, give examples of substituents

Answer 24

irreversible cyclisation of molecules that contain an electrophile and a nucleophile
check notes for mech
nucleophile=EWG=CN, NO2, COR
electrophile=LG=Cl,I,Br

Question 25

What are some general rules in irreversible cyclisation mechanism

Answer 25

attack on the electrophilic centre is Sn2 like and needs a centre of inversion for attack of sigma-star orbitals the nucleophile must be able to reach the C-LG antibonding orbital for closure to be possible

Question 26

What does the rate of ring closure depend on? and why?

Answer 26

mainly depends on ring size, 3 forms fastest, then 5 >6>>4 the entropic cost of ring closure increase with ring size because more order must be imposed the enthalpic cost of ring closure decreases with ring size because normal rings are less-strained than small rings

Question 27

What is the limitation to reversible cyclisation?

Answer 27

when molecules have both an electrophile and nucleophile and can only be used to form normal rings

Question 28

Draw mechanism for reversible cyclisation of hept2-6,dienone. give conditions

Answer 28

cyclisation process and OH elimination E1cb elim as enolate formed as cb of ketone check notes for mech

Question 29

What are 2 ways cyclopropanes can be made?

Answer 29

Irreversible cyclisation or addition of carbenes to alkenes

Question 30

What is a carbene

Answer 30

carbenes contain a neutral carbon with 2 valence electrons and two unshared they might have a singlet or triplet ground state depending on substituents singlet if R halogen, triplet of R alkyl/aryl

Question 31

show how a singlet carbene can be generated and reacted with alkene, draw simple mechanism

Answer 31

generated via alpha elimination, react spontaneously with alkenes where alkene geometry is retained carbenes are electrophilic so react preferably with electron rich alkenes mech in notes

Question 32

how can a triplet carbene be generated and reacted? Draw mech

Answer 32

generated through decomposition of diazo compounds, react in stepwise way so alkene geometry not often retained in product

Question 33

What are carbenoids

Answer 33

metal-bound species that exhibits carbene like reactivity but often more stable and selective than free carbenes

Question 34

give an example of carbenoids reacting to show selectivity effects

Answer 34

with an OSiMe3 substituent attached to alkene carbon, makes carbenoid electron rich, so reaction would be preferred on this alkene than an electron neutral alkene

Question 35

What are three ways of epoxide synthesis?

Answer 35

irreversible cyclisation, Weitz-Scheffer reaction or by reacting alkene + peracid

Question 36

What is the Weitz-Scheffer reaction? Draw mechanism

Answer 36

way of epoxide formation electron deficient alkene required, Sn2 like reaction on the O centre. H2O2 deprotonated and attacks carbonyl from EWG.... check mech

Question 37

explain some of the properties of bonding in epoxides

Answer 37

epoxides have high Pitzer and Baeyer strain, the C-O bonds are polarised due to electronegativity differences, the C-O bonds are weak due to their high p-orbital character

Question 37

Explain how epoxides made from alkene and peracid (mCBPA). Draw simple mechanism

Answer 37

peracids like mCBPA ae electrophilic oxidants so they only react with electron neutral or electron rich alkenes reaction is in a single step (forming TS) so geometry retained in product

Question 38

how do epoxides open under acidic conditions? show mech

Answer 38

Sn2 mechanism with Sn1 character, proceeds via attack at the site better able to support developing positive charge doesnt require a reactive nucleophile

Question 39

how do epoxides open under basic conditions? show mech

Answer 39

through Sn2 reaction, proceeds via attack at least hindered site, requires a reactive nucleophile

Question 40

how can regioselectivity of epoxide opening reactions be controlled

Answer 40

through choice of acidic/basic conditions. Substituents upon opening will have anti-stereochemistry

Question 41

How can cyclobutanes be prepared?

Answer 41

Via irreversible cyclisation or by [2+2]cycloaddition under irradiation

Question 42

What is Robinsons annulation used for? Draw quick mechanism

Answer 42

used for synthesis of 6 membered rings

Question 43

What is the Diels-Alder reaction used for? draw mechanism

Answer 43

[4+2] addition, used for synthesis of six membered rings, thermally allowed upon heating, geometry retained in product but diene starting material needs to be cis for reaction

Question 44

What is the birch reduction? show mech

Answer 44

reduction of benzene by series of electron transfer. double bond position depends on nature of substituents

Question 45

Draw the mechanism of the formation of cyclic acetals

Answer 45

all steps are reversible so thermodynamic product is formed (most stable product) starts with diol, with a stereocentre check notes for mech

Question 46

Explain Sn2 substitution reactions of cyclohexyl halides and the way its rates can very

Answer 46

rate of Sn2 substitution of cyclohexyl halides is effected by steric hindrance to approach of the nucleophile anti-diastereoisomer (attack from top) has H hinderance getting in the way of the antibonding C-LG orbital so slower reaction but syn-diastereoisomer (Nu- attack from below) has less H hinderance so much quicker.

Question 47

Describe 1,2-Addition of cyclohexanones.

Answer 47

they have one sp2 centre so can adopt a chair conformation meaning it can undergo axial or equatorial attack. the selectivity of addition depends on size of nucleophile, small nucleophiles preferer axial attack as they are unaffected by the H hinderance larger Nu prefer equatorial attack

Question 48

Describe enolate alkylation. How can we know which products are minor/major

Answer 48

enolate formed from cyclohexanone 6MRs with 2 sp2 centres adopt a half-chair conformation and the a twist boat as a transition state. strong base such as LDA used. if upper/lower attack preferred depends on the energy of the twist boat TS showing major product as lowest energy TS

Question 49

Draw a mechanism of enolate alkylation showing minor and major products

Answer 49

check notes for mechanism

Question 50

With cyclohexenes/twist boat TS, which transition states are preferred giving the major product?

Answer 50

Kinetically controlled so always the transition state with the lowest energy state even if the product if thermodynamically unfavourable

Question 51

What is the preferred transition state with cyclohexenone?

Answer 51

can form twist boat or chair-like conformation, chair like is lower in Energy so chair-like TS preferred.